Of mammalian cytoplasmic aldo-keto reductases, the rat liver aldehyde reductase is a soluble constitutive enzyme with a wide substrate spectrum. The only significant ketone substrate for this enzyme is daunorubicin. The amino sugar group is important in the mechanism of this reaction. "Site specific free radicals" are postulated as the active form of several anticancer antibiotics. The quinone antibiotics, adriamycin, daunorubicin streptonigrin and mitomycin C and the quinoid, actinomycin D are all activated to free radical state by mammalian microsomes or the microsomal enzyme, NADPH Cytochrome P 450 reductase. The free radical forms of these agents offer a new mechanism by which the DNA damage, other macromolecular damage, and cytotoxicity can be explained.